Sorafenib Tosylate and Erlotinib Hydrochloride in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gallbladder Cancer or Cholangiocarcinoma

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Unresectable Gallbladder Carcinoma; Gallbladder Adenocarcinoma With Squamous Metaplasia; Recurrent Extrahepatic Bile Duct Carcinoma; Gallbladder Adenocarcinoma; Undifferentiated Gallbladder Carcinoma; Recurrent Gallbladder Carcinoma; Unresectable Extrahepatic Bile Duct Carcinoma; Hilar Cholangiocarcinoma; Extrahepatic Bile Duct Adenocarcinoma

Treatments: Drug: Erlotinib Hydrochloride; Drug: Sorafenib Tosylate

Study type: Interventional

Funder types: NIH

Identifiers

NCT01093222

CDR0000668246

NCI-2011-02027 (Registry Identifier)

S0941 (Other Identifier)

SWOG-S0941

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This phase II trial is studying how well giving sorafenib tosylate together with erlotinib hydrochloride works in treating patients with locally advanced, unresectable, or metastatic gallbladder cancer or cholangiocarcinoma. Sorafenib tosylate and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

Full description

OBJECTIVES:

I. To assess the progression-free survival in patients with unresectable or metastatic gallbladder carcinoma or cholangiocarcinoma treated with the combination of sorafenib (sorafenib tosylate) and erlotinib (erlotinib hydrochloride).

II. To assess the overall survival in patients with unresectable or metastatic gallbladder carcinoma or cholangiocarcinoma treated with the combination of sorafenib and erlotinib.

III. To assess the objective response rate. IV. To assess the frequency and severity of toxicities. V. To collect specimens for banking for future research.

OUTLINE: This is a multicenter study.

Patients receive sorafenib tosylate orally (PO) twice daily and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 6 months for 3 years.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Cytologically or pathologically confirmed gallbladder carcinoma or cholangiocarcinoma

  • No ampullary carcinoma

• Locally advanced unresectable or distant metastatic disease

• Measurable disease

• Patients with biliary obstruction must have decompression of the biliary tree by ERCP and stenting or percutaneous drainage

• No prior systemic treatment for metastatic or unresectable locally advanced disease

• No known brain metastases

• Zubrod performance status of 0-1

• Leukocyte count ≥ 3,000/mm^3

• ANC ≥ 1,000/mm^3

• Platelet count ≥100,000/mm^3

• Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN)

  • For patient who had decompression of the biliary tree within the past 14 days, stability of the bilirubin level needs to be confirmed with two measurements within 5 to 7 days of each other

• Serum albumin ≥ 2.5 g/dL

• AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN for liver metastases)

• Creatinine clearance ≥ 60 mL/min

• Not pregnant or nursing

• Fertile patients must agree to use effective contraception

• No active biliary sepsis

• No bleeding diathesis

• No uncontrolled or clinically significant cardiovascular disease, including any of the following:

  • Myocardial infarction within the past 6 months
  • Uncontrolled angina within the past 6 months
  • NYHA class II-IV congestive heart failure
  • Grade 3 cardiac valve dysfunction
  • Cardiac arrhythmia not controlled by medication
  • History of stroke or transient ischemic attack within the past 6 months
  • History of arterial thrombotic event of any type in the past 6 months

• No uncontrolled hypertension, as evidenced by systolic BP ≥ 150 mm Hg or diastolic BP ≥ 100 mm Hg, within the past 28 days

• Must be able to swallow and tolerate oral medications

  • No gastrointestinal tract disease or prior abdominal surgery that results in an inability to absorb oral medication

• No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free within the past 3 years

• No concurrent grapefruit or its juice

• At least 6 months since 1 adjuvant or neoadjuvant regimen of chemotherapy, hormonal therapy, immunotherapy, radiotherapy (to < 25% of bone marrow only), or chemoradiotherapy before documented recurrence or metastatic disease

• No prior treatment with any antiangiogenic agent or any EGFR inhibitors for any reason

• Concurrent multiple anti-hypertensive medications allowed

• No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other therapy, including herbal or alternative medications for treatment of cancer

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

Treatment (sorafenib tosylate and erlotinib hydrochloride)

Experimental group

Description:

Patients receive sorafenib tosylate PO twice daily and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: Sorafenib Tosylate

Drug: Erlotinib Hydrochloride